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11 results on '"Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA)"'

1. Transesophageal echocardiography for cardiovascular risk estimation in patients with sepsis and new-onset atrial fibrillation: a multicenter prospective pilot study

Author

Labbé, Vincent, Ederhy, Stephane, Lapidus, Nathanael, Joffre, Jérémie, Razazi, Keyvan, Laine, Laurent, Sy, Oumar, Voicu, Sebastian, Chemouni, Frank, Aissaoui, Nadia, Smonig, Roland, Doyen, Denis, Carrat, Fabrice, Voiriot, Guillaume, Mekontso-Dessap, Armand, Cohen, Ariel, Fartoukh, Muriel, Guidet, Bertrand, Ait-Oufella, Hafid, Bourcier, Simon, da Silva, Daniel, Jochmans, Sebastien, Dellamonica, Jean, Timsit, Jean-François, Megarbane, Bruno, Diehl, Jean-Luc, Rushton-Smith, Sophie, Service de Réanimation et USC Médico-Chirurgicale = Médecine intensive réanimation [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, Département Médico-Universitaire APPROCHES, Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Thrombose, atherothrombose et pharmacologie appliquée, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier de Melun (CHM), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Gustave Roussy (IGR), Département d'anesthésie, réanimation et pathologie infectieuse (DARPI), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Nice (CHU Nice), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), HAL-SU, Gestionnaire, Service de Réanimation et USC Médico-Chirurgicale [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Melun, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Université Paris Descartes - Paris 5 (UPD5), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Sorbonne Université - Faculté de Médecine (SU FM), FAST Study Group: Bertrand Guidet, Hafid Ait-Oufella, Simon Bourcier, Daniel Da Silva, Sebastien Jochmans, Jean Dellamonica, Jean-François Timsit, Bruno Megarbane, Jean-Luc Diehl, Sophie Rushton-Smith, and WEISS, Nicolas

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Atrial fibrillation Transesophageal echocardiography Stroke Bleeding Sepsis, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Anesthesiology, medicine, 030212 general & internal medicine, cardiovascular diseases, Thrombus, Transesophageal echocardiography, Stroke, RC86-88.9, business.industry, Septic shock, Research, Incidence (epidemiology), Hazard ratio, Bleeding, Medical emergencies. Critical care. Intensive care. First aid, Atrial fibrillation, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Cardiology, cardiovascular system, business
Abstract

Background Echocardiographic parameters have been poorly investigated for estimating cardiovascular risk in patients with sepsis and new-onset atrial fibrillation. We aim to assess the prevalence of transesophageal echocardiographic abnormalities and their relationship with cardiovascular events in mechanically ventilated patients with sepsis and new-onset atrial fibrillation. Methods In this prospective multicenter pilot study, left atrial/left atrial appendage (LA/LAA) dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were assessed using an initial transesophageal echocardiographic study, which was repeated after 48–72 h to detect LA/LAA thrombus formation. The study outcome was a composite of cardiovascular events at day 28, including arterial thromboembolic events (ischemic stroke, non-cerebrovascular arterial thromboembolism, LA/LAA thrombus), major bleeding, and all-cause death. Results The study population comprised 94 patients (septic shock 63%; 35% women; median age 69 years). LA/LAA dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were detected in 17 (19%), 22 (24%), and 27 (29%) patients, respectively. At day 28, the incidence of cardiovascular events was 46% (95% confidence interval [CI]: 35 to 56). Arterial thromboembolic events and major bleeding occurred in 7 (7%) patients (5 ischemic strokes, 1 non-cerebrovascular arterial thromboembolism, 2 left atrial appendage thrombi) and 18 (19%) patients, respectively. At day 28, 27 patients (29%) died. Septic shock (hazard ratio [HR]: 2.36; 95% CI 1.06 to 5.29) and left ventricular systolic dysfunction (HR: 2.06; 95% CI 1.05 to 4.05) were independently associated with cardiovascular events. Conclusions Transesophageal echocardiographic abnormalities are common in mechanically ventilated patients with sepsis and new-onset atrial fibrillation, but only left ventricular systolic dysfunction was associated with cardiovascular events at day 28.

Published
2021
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2. A meta-analysis comparing first-line immunosuppressants in neuromyelitis optica

Author

Elisabeth Maillart, Morgan McCreary, Bertrand Bourre, Su-Hyun Kim, Romain Deschamps, Xavier Ayrignac, Hélène Zéphir, Sandra Vukusic, David Laplaud, Luc Dauchet, Caroline Papeix, Benjamin Greenberg, Mikael Cohen, Romain Marignier, Aurélie Ruet, Ho Jin Kim, Jonathan Giovannelli, Nicolas Collongues, Nemos investigators, Bertrand Audoin, Jan‐Patrik Stellmann, Jonathan Ciron, Françoise Durand-Dubief, Ingo Kleiter, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Hospital of National Cancer Center [Goyang], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Ruhr University Bochum (RUB), University of Texas Southwestern Medical Center [Dallas], Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire Purpan, Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, medicine.medical_specialty, First line, medicine.medical_treatment, MEDLINE, Neurosciences. Biological psychiatry. Neuropsychiatry, Azathioprine, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, RC346-429, Research Articles, Neuromyelitis optica, business.industry, General Neuroscience, Hazard ratio, Neuromyelitis Optica, Immunosuppression, Mycophenolic Acid, medicine.disease, Meta-analysis, Rituximab, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology. Diseases of the nervous system, Neurology (clinical), business, Immunosuppressive Agents, RC321-571, medicine.drug, Research Article
Abstract

International audience; Objective : As phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta-analysis compares the efficacy of first-line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still widely used. Methods : Studies identified by the systematic review of Huang et al. (2019) were selected if they considered at least two first-line immunosuppressants among RTX, MMF, and AZA. We updated this review. The Medline, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials databases were queried between November 2018 and April 2020. To be included, the hazard ratio (HR) [95% CI] for the time to first relapse after first-line immunosuppression had to be available, calculable, or provided by the authors. Results : We gathered data from 919 NMO patients (232 RTX-, 294 MMF-, and 393 AZA-treated patients). The risk of first relapse after first-line immunosuppression was 1.55 [1.04, 2.31] (p = 0.03) for MMF compared with RTX, 1.42 [0.87, 2.30] (p = 0.16) for AZA compared with RTX, and 0.94 [0.58, 1.54] (p = 0.08) for MMF compared with AZA. Interpretation : The findings suggest that RTX is more efficient than MMF as a first-line therapy. Even if the results of our meta-analysis cannot conclude that RTX has a better efficacy in delaying the first relapse than AZA, the observed effect difference between both treatments combined with the results of previous studies using as outcome the annualized relapse rate may be in favor of RTX.

Published
2021
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3. Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study

Author

Martine El-Etr, Jérôme De Seze, Patrick Hautecoeur, Françoise Durand-Dubief, Jean Pelletier, Etienne-Emile Baulieu, Francesco Patti, David-Axel Laplaud, L. Gignoux, Maria Trojano, Emmanuelle Le Page, Sandra Vukusic, Pierre Clavelou, Luca Durelli, Iuliana Ionescu, David Brassat, Eric Berger, Catherine Cornu, Laurent Remontet, Nadine Bossard, Giovanni Castelnovo, Marc Debouverie, François Cotton, Olivier Heinzlef, Romain Marignier, Thibault Moreau, Christine Lebrun-Frenay, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service Hospitalo-Universitaire de Pharmacologie et Toxicologie - Lyon (SHUPT Lyon), Service de Biostatistiques [Lyon], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Università degli studi di Torino = University of Turin (UNITO), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Strasbourg, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHI Poissy-Saint-Germain, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Association Européenne contre les Leucodystrophies, Myelin Project, Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, Programme Hospitalier de Recherche Clinique 2005, Ministère des Affaires Sociales et de la Santé, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino (UNITO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle neurosciences [Hôpital de Purpan - Toulouse], CHU Toulouse [Toulouse], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Università degli studi di Bari Aldo Moro (UNIBA), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Nomegestrol acetate, medicine.medical_specialty, relapses, Norpregnadienes, [SDV]Life Sciences [q-bio], Relapse rate, progesterone, Gastroenterology, sex hormones, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Recurrence, Internal medicine, estradiol, Medicine, Humans, Post partum, Transdermal, business.industry, Postpartum Period, post-partum, Megestrol, medicine.disease, 17 beta estradiol, 3. Good health, Neurology, chemistry, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, 030215 immunology
Abstract

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. Results: Recruitment was stopped prematurely due to slow inclusions ( n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58–1.39), placebo = 0.97 (0.63–1.50) ( p = 0.79)). Conclusion: POPARTMUS failed showing efficacy of a NOMAc–E2 combination in preventing post-partum relapses.

Published
2021
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4. Is COVID‐19 infection more severe in kidney transplant recipients?

Author

Nathalie Chavarot, Bruno Moulin, Valérie Moal, Olivier Thaunat, Marc Hazzan, Jamal Bamoulid, Antoine Durrbach, Christiane Mousson, Nassim Kamar, Yannick Lemeur, Charlotte Kaeuffer, Clarisse Greze, Philippe Grimbert, Ilies Benotmane, Dominique Bertrand, Antoine Thierry, Tristan Legris, Gilles Blancho, Pierre François Westeel, Mariam Jdidou, Hélène François, Sophie Caillard, Marie Matignon, Yvon Ruch, Morgane Solis, Antoine Sicard, Dany Anglicheau, Philippe Gatault, Valentin Goutaudier, François Danion, Lionel Couzi, Charlotte Colosio, Renaud Snanoudj, Christophe Masset, Agnès Duveau, Jonathan M. Chemouny, Luc Frimat, CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Tours (UT), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Aix Marseille Université (AMU), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Bourgogne (UB), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Poitiers, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU de Bordeaux Pellegrin [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), University of Lille, This study was supported by the Strasbourg University Hospital (COVIS-HUS Study- HUS number 7760), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), AP-HP Hôpital Tenon [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University Hospital of Montpellier, Hôpital Bicêtre, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Bordeaux [Bordeaux], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Henri Mondor, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Tours, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), PINIER, CHRISTINE, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Registries, Aucun, MESH: Comorbidity, 030230 surgery, law.invention, chemistry.chemical_compound, 0302 clinical medicine, law, cardiovascular disease, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, clinical research / practice, Immunology and Allergy, Cumulative incidence, Pharmacology (medical), kidney transplantation / nephrology, MESH: Incidence, MESH: Aged, Univariate analysis, MESH: France / epidemiology, MESH: Middle Aged, MESH: Transplant Recipients / statistics & numerical data, Acute kidney injury, Intensive care unit, 3. Good health, MESH: COVID-19 / epidemiology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, glomerular filtration rate (GFR), kidney failure / injury, medicine.medical_specialty, infection and infectious agents - viral, infectious disease, Brief Communication, MESH: Graft Rejection / prevention & control, 03 medical and health sciences, Internal medicine, Diabetes mellitus, MESH: Severity of Illness Index, MESH: COVID-19 / diagnosis, medicine, Humans, MESH: SARS-CoV-2, Mechanical ventilation, Creatinine, Transplantation, MESH: Humans, business.industry, SARS-CoV-2, MESH: Graft Rejection / epidemiology, COVID-19, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, Transplant Recipients, MESH: Male, immunosuppressive regimens, MESH: Immunosuppressive Agents / therapeutic use, MESH: Pandemics, MESH: Propensity Score, chemistry, Reinfection, MESH: Immunosuppression / methods, MESH: Intensive Care Units, business, MESH: Female, MESH: Kidney Transplantation
Abstract

International audience; There are no studies which have compared the risk of severe Covid-19 and related mortality between transplant recipients and non-transplant patients. We enrolled two groups of patients hospitalized for Covid-19, i.e., kidney transplant recipients from the French Registry of Solid Organ Transplant (n=306) and a single-center cohort of non-transplant patients (n=795). An analysis was performed among subgroups matched for age and risk factors for severe Covid-19 or mortality. Severe Covid-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death.Transplant recipients were younger and had more comorbidities compared to non-transplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe Covid-19 did not differ between KTR and non-transplant patients; however, 30-day Covid-19-related mortality was significantly higher in KTR (17.9% versus 11.4%, respectively, p=0.038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe Covid-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR=1.55), and creatinine level >115 µmol/L (HR=2.32) were associated with Covid-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. Kidney transplant recipients had a higher Covid-19-related mortality compared to non-transplant hospitalized patients.

Published
2021
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5. Menstrual Toxic Shock Syndrome: A French Nationwide Multicenter Retrospective Study

Author

Damien Contou, Gwenhaël Colin, Brendan Travert, Sébastien Jochmans, Marie Conrad, Jean-Baptiste Lascarrou, Benoit Painvin, Alexis Ferré, David Schnell, Béatrice La Combe, Rémi Coudroy, Stephan Ehrmann, Jérôme Rambaud, Arnaud Wiedemann, Pierre Asfar, Pierre Kalfon, Emmanuel Guérot, Sébastien Préau, Laurent Argaud, Florence Daviet, Jean Dellamonica, Audrey Dupont, Muriel Fartoukh, Toufik Kamel, Gaetan Beduneau, Florence Canouï-Poitrine, Emmanuelle Boutin, Gérard Lina, Armand Mekontso Dessap, Anne Tristan, Nicolas de Prost, French m-TSS Study Group, Centre Hospitalier Victor Dupouy, CH Départemental Vendée, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier de Melun (CHM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Laboratoire Lasers, Plasmas et Procédés photoniques (LP3), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier d'Angoulême (CH Angoulême), Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis [CHU Limoges] (Réseau CRICS-TRIGGERSEP ), Hôpital Dupuytren [CHU Limoges], Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Réanimation polyvalente [Chartres], Hôpital Louis Pasteur [Chartres], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation (ORLEANS - Réa), Centre Hospitalier Régional d'Orléans (CHRO), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, CarMeN, laboratoire, Centre Hospitalier de Melun, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10

Subjects
0301 basic medicine, Microbiology (medical), Adult, Staphylococcus aureus, medicine.medical_specialty, Adolescent, genetic structures, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030106 microbiology, Disease, law.invention, Sepsis, Menstruation, sepsis, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Intensive care, medicine, Humans, 030212 general & internal medicine, Child, menstrual toxic shock syndrome, Retrospective Studies, Superantigens, Critically ill, business.industry, Medical record, Tracheal intubation, Toxic shock syndrome, Retrospective cohort study, Staphylococcal Infections, tampon, bacterial infections and mycoses, Institutional review board, medicine.disease, Shock, Septic, Intensive care unit, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Infectious Diseases, Icu, Female, Observational study, menstruation, business
Abstract

Background Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking. Methods This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between 1 January 2005 and 31 December 2020 in 43 French pediatric (n = 7) or adult (n = 36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as to assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, in critically ill patients with m-TSS. Results In total, 102 patients with m-TSS (median age, 18 years; interquartile range, 16–24 years) were admitted to 1 of the participating ICUs. All blood cultures (n = 102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for superantigenic toxin gene sequences was performed for 76 of the 92 vaginal samples positive for S. aureus (83%), and toxic shock syndrome toxin 1 was isolated from 66 strains (87%). At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS, and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with antitoxin antibiotic therapy, and 8 (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors, and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU. Conclusions In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.

Published
2021
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6. Th17-Immune Response in Patients With Membranous Nephropathy Is Associated With Thrombosis and Relapses

Author

Marion Cremoni, Vesna Brglez, Sandra Perez, Fabrice Decoupigny, Kévin Zorzi, Marine Andreani, Alexandre Gérard, Sonia Boyer-Suavet, Caroline Ruetsch, Sylvia Benzaken, Vincent Esnault, Barbara Seitz-Polski, Service de Néphrologie-Dialyse-Transplantation, CHU de Nice, Université Côte d'Azur, France, Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre de Référence Maladies Rares « Syndrome Néphrotique Idiopathique de l’Enfant et de l’Adulte », Études des Structures, des Processus d’Adaptation et des Changements de l’Espace (ESPACE), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Avignon Université (AU)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire d’Immunologie [CHU Nice], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Avignon Université (AU)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
0301 basic medicine, Male, medicine.medical_treatment, 030232 urology & nephrology, Anti-Inflammatory Agents, Glomerulonephritis, Membranous, 0302 clinical medicine, Recurrence, Risk Factors, 11. Sustainability, Medicine, Immunology and Allergy, Prospective Studies, Cells, Cultured, health care economics and organizations, Original Research, relapse, Venous Thromboembolism, [SHS.GEO]Humanities and Social Sciences/Geography, Middle Aged, Thrombosis, 3. Good health, Cytokine, Cytokines, Environmental Pollutants, Female, medicine.symptom, Rituximab, lcsh:Immunologic diseases. Allergy, Adult, Immunology, education, Inflammation, fine air particulate matter, Risk Assessment, 03 medical and health sciences, Immune system, Membranous nephropathy, Humans, In patient, Relapse risk, thrombosis, Aged, business.industry, Non invasive biomarkers, non-invasive biomarker, Urban Health, membranous nephropathy, Environmental Exposure, medicine.disease, [SDE.ES]Environmental Sciences/Environmental and Society, 030104 developmental biology, inflammation, Th17-profile, Case-Control Studies, Th17 Cells, Particulate Matter, prognosis, business, lcsh:RC581-607, Biomarkers
Abstract

Membranous nephropathy (MN) is a rare autoimmune kidney disease. Most autoimmune diseases are associated with a pro-inflammatory Th17-immune response, but little is known about immune dysregulation in MN. In China, MN was associated with exposure to fine air particulate matter (PM2.5) that could act as a danger signal and redirect immune response toward the Th2 or Th17 pathway. We aimed to analyze the cytokine profile of MN patients and to study the possible environmental factors involved in this immune reorientation, as well as the consequences on the prognosis of the disease. In this prospective study, 59 MN patients filled a comprehensive lifestyle questionnaire. Peripheral blood cells from MN patients were stimulated in vitro to measure the cytokines produced in supernatant. Cytokine profiles of MN patients were compared to 28 healthy donors and analyzed regarding individual PM2.5 exposure. Compared to healthy donors, MN patients had higher serum levels of Th17 and Th2 cytokines IL-17A (62 pg/ml [IQR, 16–160] versus 31 [IQR, 13–51], P=0.035), IL-6 (66767 pg/ml [IQR, 36860–120978] versus 27979 [IQR, 18672–51499], P=0.001), and IL-4 (12 pg/ml [IQR, 0–33] versus 0 pg/ml [IQR, 0–0], P=0.0003), respectively, as well as a deficiency of Th1 and regulatory T cell cytokines IFN-γ (5320 pg/ml [IQR, 501–14325] versus 18037 [IQR, 4889–31329], P=0.0005) and IL-10 (778 pg/ml [IQR, 340–1247] versus 1102 [IQR, 737–1652], P=0.04), respectively. MN patients with high IL-17A levels lived in areas highly exposed to PM2.5: 51 μg/m3 versus 31 μg/m3 for patients with low IL-17A levels (P=0.002) while the World Health Organization recommends an exposition below 10 μg/m3. MN patients with Th17-mediated inflammation had more venous thromboembolic events (P=0.03) and relapsed more often (P=0.0006). Rituximab treatment induced Th1 and regulatory T cell cytokines but did not impact Th17 cytokines. MN patients with Th17-mediated inflammation which appears to be related to an urban environment have worse prognosis. Alternative strategies targeting dysregulated cytokine balance could be considered for these patients at high risk of relapse.

Published
2020
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7. T-piece versus pressure-support ventilation for spontaneous breathing trials before extubation in patients at high risk of reintubation: protocol for a multicentre, randomised controlled trial (TIP-EX)

Author

Jean-Paul Mira, Jeremy Bourenne, Agathe Delbove, René Robert, Gaetan Beduneau, Jean-Pierre Frat, Jérôme Devaquet, Arnaud Gacouin, Laurence Dangers, Nicolas Terzi, Stéphanie Ragot, Guylaine Labro, Antoine Romen, Gael Pradel, Christophe Leroy, Jean Reignier, Laurent Argaud, Rémi Coudroy, Quentin Levrat, Stephan Ehrmann, Jean-Pierre Quenot, Emmanuel Vivier, Guillaume Lacave, Christophe Guitton, Marie-Ange Azais, Alexandre Lautrette, Mai-Anh Nay, Anahita Rouzé, Damien Contou, Martin Dres, Gwenaël Prat, Jean Dellamonica, Arnaud W. Thille, Nicholas Sedillot, Béatrice Lacombe, Université de Lille, CNRS, Centre hospitalier universitaire de Poitiers [CHU Poitiers], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours [CHRU Tours], Centre Hospitalier Victor Dupouy, Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre hospitalier de Pau, Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier de Versailles André Mignot [CHV], CHU Dijon, CIC - CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] [CHU], CHRU Brest - Service de Réanimation Médicale [CHU - BREST - Réa Med], Centre Hospitalier Emile Muller [Mulhouse] [CH E.Muller Mulhouse], Centre hospitalier universitaire de Nantes [CHU Nantes], Service d'anesthésie et réanimation chirurgicale [Nantes], Service de réanimation médicale [CHU Rouen], Centre Hospitalier Universitaire de Nice [CHU Nice], Centre Hospitalier Régional d'Orléans [CHRO], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Centre hospitalier Bretagne Atlantique (Morbihan) [CHBA], Hôpital Cochin [AP-HP], Hôpital de la Timone [CHU - APHM] [TIMONE], Centre Jean Perrin [Clermont-Ferrand] [UNICANCER/CJP], Hôpital Edouard Herriot [CHU - HCL], Hôpital Foch [Suresnes], Centre hospitalier Saint Joseph - Saint Luc [Lyon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon [CHD Vendée], Centre Hospitalier Emile Roux [AP-HP], INSERM CIC 0802 [INSERM - CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Félix-Guyon [Saint-Denis, La Réunion, France], Centre Hospitalier de Versailles André Mignot (CHV), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Groupe Hospitalier Bretagne Sud (GHBS), Centre Hospitalier Henri Mondor d'Aurillac, Unité de soins intensifs médicaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHRU Brest - Service de Réanimation Médicale (CHU - BREST - Réa Med), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Hospitalier Fleyriat [Bourg en Bresse], Unité de Soins Intensifs [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Hospices Civils de Lyon (HCL), Centre Hospitalier de La Rochelle (CHR), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), REVA research network, CarMeN, laboratoire, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pressure support ventilation, law.invention, Spontaneous breathing trial, Positive-Pressure Respiration, 03 medical and health sciences, Work of breathing, 0302 clinical medicine, Randomized controlled trial, law, Informed consent, medicine, respiratory medicine (see thoracic medicine), Humans, 030212 general & internal medicine, adult intensive & critical care, respiratory physiology, Mechanical ventilation, business.industry, Intensive Care, General Medicine, Intensive care unit, Respiration, Artificial, 3. Good health, [SDV] Life Sciences [q-bio], 030228 respiratory system, Anesthesia, Breathing, Airway Extubation, Medicine, France, business, Ventilator Weaning
Abstract

IntroductionIn intensive care unit (ICU), the decision of extubation is a critical time because mortality is particularly high in case of reintubation. To reduce that risk, guidelines recommend to systematically perform a spontaneous breathing trial (SBT) before extubation in order to mimic the postextubation physiological conditions. SBT is usually performed with a T-piece disconnecting the patient from the ventilator or with low levels of pressure-support ventilation (PSV). However, work of breathing is lower during PSV than during T-piece. Consequently, while PSV trial may hasten extubation, it may also increase the risk of reintubation. We hypothesise that, compared with T-piece, SBT performed using PSV may hasten extubation without increasing the risk of reintubation.Methods and analysisThis study is an investigator-initiated, multicentre randomised controlled trial comparing T-piece vs PSV for SBTs in patients at high risk of reintubation in ICUs. Nine hundred patients will be randomised with a 1:1 ratio in two groups according to the type of SBT. The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without invasive mechanical ventilation between the initial SBT (day 1) and day 28. Secondary outcomes include the number of days between the initial SBT and the first extubation attempt, weaning difficulty, the number of patients extubated after the initial SBT and not reintubated within the following 72 hours, the number of patients extubated within the 7 days following the initial SBT, the number of patients reintubated within the 7 days following extubation, in-ICU length of stay and mortality in ICU, at day 28 and at day 90.Ethics and disseminationThe study has been approved by the central ethics committee ‘Ile de France V’ (2019-A02151-56) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04227639.

Published
2020
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8. BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS

Author

Eric Berger, Clarisse Carra, Christine Lebrun-Frenay, Patrick Vermersch, Chrystelle Cappé, Gilles Defer, Béatrice Pignolet, David Brassat, Marc Debouverie, Bruno Brochet, Lydiane Mondot, Aurélie Ruet, Hélène Zéphir, Nathalie Derache, Guillaume Mathey, Kévin Bigaut, Sandrine Wiertlewski, Jérôme De Seze, David-Axel Laplaud, Mikael Cohen, Pierre Labauge, Florence Bucciarelli, Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Pôle neurosciences [Hôpital de Purpan - Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Ressources et de Compétences Sclérose en Plaques (CRCSEP), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Projet Fédératif Hospitalo-Universitaire IMmune-Mediated INflammatory diseases aNd Targeted Therapies [Lille] (FHU IMMINeNT), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg

Subjects
Oncology, medicine.medical_specialty, Head to head, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, natalizumab, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, therapeutics, Humans, magnetic resonance imaging, Prospective Studies, 030212 general & internal medicine, fingolimod, medicine.diagnostic_test, Fingolimod Hydrochloride, business.industry, Magnetic resonance imaging, medicine.disease, Fingolimod, 3. Good health, Neurology, Neurology (clinical), Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS) Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing–remitting MS Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity. Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029). Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing–remitting MS. Our results suggest a superiority of NTZ over FTY.

Published
2020
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9. Effects on Melanoma Cell Lines Suggest No Significant Risk of Melanoma Under Cladribine Treatment

Author

Sophie Tartare-Deckert, Mikael Cohen, Berestjuk I, Christine Lebrun-Frenay, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), TARTARE-DECKERT, Sophie, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)

Subjects
[SDV]Life Sciences [q-bio], Purine analogue, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, 030212 general & internal medicine, Significant risk, RC346-429, Cladribine, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Melanoma, business.industry, Cell growth, Brief Report, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Immunosuppressors, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Neurology, Mechanism of action, Melanoma cell line, Cancer research, Neurology. Diseases of the nervous system, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

International audience; Cladribine is an oral synthetic purine analog that depletes lymphocytes and induces a dose-dependent reduction of T and B cells. It was approved for the therapy of highly active relapsing-remitting multiple sclerosis. Given cladribine's mechanism of action, an increased risk of malignancies was suspected from the number of cancers that occurred in the 3.5 mg/kg-treated arm (CLARITY study). We showed that cladribine inhibits cell proliferation on three melanoma cell lines tested, irrespectively of their mutational oncogenic status and invasive/metastatic potential. Aggregated safety data demonstrated that the risk of melanoma is not confirmed.

Published
2020
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10. Outcome and risk of recurrence in a large cohort of idiopathic longitudinally extensive transverse myelitis without AQP4/MOG antibodies

Author

Caroline Papeix, Gwenaelle Runavot, Françoise Durand-Dubief, Sandra Vukusic, Christine Lebrun-Frenay, Elisabeth Maillart, Pierre Labauge, Jonathan Ciron, Nomadmus study groups, Philippe Kerschen, Bertrand Bourre, Jérôme De Seze, Alexis Montcuquet, Nathalie Derache, Mikael Cohen, Romain Marignier, Bertrand Audoin, Romain Deschamps, Céline Louapre, Clarisse Carra-Dalliere, Hélène Zéphir, Sandrine Wiertlewski, Sfsep Ofsep, David Laplaud, Nicolas Collongues, Nawel Hadhoum, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hospices Civils de Lyon, Departement de Neurologie (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Rouen, Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Toulouse [Toulouse], CHU Strasbourg, Centre de Ressources et de Compétences Sclérose en Plaques (CRCSEP), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), CHU Lille, Fondation Ophtalmologique Adolphe de Rothschild [Paris], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Limoges, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Sud Saint Pierre [Ile de la Réunion], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Male, Neurology, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease, Transverse myelitis, lcsh:RC346-429, Cohort Studies, 0302 clinical medicine, Recurrence, Risk Factors, Outcome, First episode, Aged, 80 and over, biology, General Neuroscience, Immunoglobulins, Intravenous, Plasmapheresis, Middle Aged, Prognosis, Neuromyelitis optica, 3. Good health, Natural history, Immunosuppressive drug, Female, Immunosuppressive Agents, Adult, Seronegative, medicine.medical_specialty, Adolescent, Immunology, Myelitis, Transverse, Myelin oligodendrocyte glycoprotein, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Internal medicine, medicine, Humans, lcsh:Neurology. Diseases of the nervous system, Aged, Autoantibodies, Aquaporin 4, Longitudinally extensive transverse myelitis, business.industry, Research, Recovery of Function, medicine.disease, Treatment, 030104 developmental biology, biology.protein, Myelin-Oligodendrocyte Glycoprotein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Longitudinally extensive transverse myelitis (LETM) is classically related to aquaporin (AQP4)-antibodies (Ab) neuromyelitis optica spectrum disorders (NMOSD) or more recently to myelin oligodendrocyte glycoprotein (MOG)-Ab associated disease. However, some patients remain negative for any diagnosis, despite a large work-up including AQP4-Ab and MOG-Ab. Data about natural history, disability outcome, and treatment are limited in this group of patients. We aimed to (1) describe clinical, biological, and radiological features of double seronegative LETM patients; (2) assess the clinical course and identify prognostic factors; and (3) assess the risk of recurrence, according to maintenance immunosuppressive therapy. Methods Retrospective evaluation of patients with a first episode of LETM, tested negative for AQP-Ab and MOG-Ab, from the French nationwide observatory study NOMADMUS. Results Fifty-three patients (median age 38 years (range 16–80)) with double seronegative LETM were included. Median nadir EDSS at onset was 6.0 (1–8.5), associated to a median EDSS at last follow-up of 4.0 (0–8). Recurrence was observed in 24.5% of patients in the 18 following months, with a median time to first relapse of 5.7 months. The risk of recurrence was lower in the group of patients treated early with an immunosuppressive drug (2/22, 9%), in comparison with untreated patients (10/31, 32%). Conclusions A first episode of a double seronegative LETM is associated to a severe outcome and a high rate of relapse in the following 18 months, suggesting that an early immunosuppressive treatment may be beneficial in that condition.

Published
2020
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11. Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab

Author

Fissolo, Nicolás, Pignolet, Beatrice, Rio, Jordi, Vermersch, Patrick, Ruet, Aurélie, deSèze, Jerome, Labauge, Pierre, Vukusic, Sandra, Papeix, Caroline, Martinez-Almoyna, Laurent, Tourbah, Ayman, Clavelou, Pierre, Moreau, Thibault, Pelletier, Jean, Lebrun-Frenay, Christine, Bourre, Bertrand, Defer, Gilles, Montalban, Xavier, Brassat, David, Comabella, Manuel, Universitat Autònoma de Barcelona, Universitat Autònoma de Barcelona (UAB), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vall d'Hebron University Hospital [Barcelona], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [Aix-en-Provence], Centre Hospitalier du Pays d'Aix, Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de Psychopathologie et Neuropsychologie (LPN), Université Paris 8 Vincennes-Saint-Denis (UP8), CHU Clermont-Ferrand, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Nice (CHU Nice), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), CHU Rouen, Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre d'Esclerosi Múltiple de Catalunya (CemCat), Vall d’Hebron Research Institute (VHIR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Lille Neurosciences & Cognition - U 1172 (LilNCog), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), CHU Bordeaux [Bordeaux], Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Service de Neurologie [Lyon], CHU Lyon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie [Reims], Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), HAL-SU, Gestionnaire, Institut Català de la Salut, [Fissolo N, Comabella M] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Pignolet B] CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse, CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France. [Rio J, Montalban X] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Vermersch P] Univ. Lille, Inserm U1172, CHU Lille, FHU Imminent, France. [Ruet A] CHU de Bordeaux, INSERM-CHU CIC-P 0005, Service de Neurologie, Bordeaux F-33076, France. Université de Bordeaux, Bordeaux F-33076, France. [deSèze J] Department of Neurology, Hôpital Civil, Strasbourg, Vall d'Hebron Barcelona Hospital Campus, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Oncology, Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Neurofilament Proteins [CHEMICALS AND DRUGS], viruses, Other subheadings::Other subheadings::/drug therapy [Other subheadings], MESH: Multiple Sclerosis, Relapsing-Remitting / blood, 0302 clinical medicine, Natalizumab, Neurofilament Proteins, 030212 general & internal medicine, Prospective cohort study, MESH: Middle Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], MESH: Multiple Sclerosis / diagnosis, virus diseases, MESH: Follow-Up Studies, Middle Aged, Prognosis, Clinical Practice, MESH: Immunologic Factors / administration & dosage, Neurology, MESH: Young Adult, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Multiple Sclerosis / drug therapy, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Otros calificadores::Otros calificadores::Otros calificadores::/sangre [Otros calificadores], medicine.drug, Adult, medicine.medical_specialty, Neurofilament, MESH: Multiple Sclerosis, Relapsing-Remitting / diagnosis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Filaments citoplasmàtics, sustancias macromoleculares::polímeros::biopolímeros::proteínas de filamentos intermedios::proteínas de neurofilamentos [COMPUESTOS QUÍMICOS Y DROGAS], Sensitivity and Specificity, Article, MESH: Prognosis, Multiple sclerosis, Young Adult, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, parasitic diseases, MESH: Leukoencephalopathy, Progressive Multifocal / blood, medicine, Humans, Immunologic Factors, Other subheadings::Other subheadings::/blood [Other subheadings], In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Leukoencephalopathy, Progressive Multifocal / diagnosis, MESH: Humans, business.industry, MESH: Multiple Sclerosis / blood, MESH: Adult, medicine.disease, MESH: Sensitivity and Specificity, MESH: Male, Class I, Avaluació de resultats (Assistència sanitària), MESH: Multiple Sclerosis, Relapsing-Remitting / drug therapy, Neurology (clinical), business, Esclerosi múltiple - Tractament, MESH: Female, MESH: Natalizumab / administration & dosage, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Follow-Up Studies, MESH: Neurofilament Proteins / blood
Abstract

ObjectivesThe study aimed to assess the potential for serum neurofilament light chain (NFL) levels to predict the risk of progressive multifocal leukoencephalopathy (PML) in natalizumab (NTZ)-treated patients with multiple sclerosis (MS) and to discriminate PML from MS relapses.MethodsNFL levels were measured with single molecule array (Simoa) in 4 cohorts: (1) a prospective cohort of patients with MS who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr); (2) a cohort of patients whose blood was collected during PML; (3) an independent cohort of non-PML NTZ-treated patients with serum NFL determinations at 2 years (replication cohort); and (4) a cohort of patients whose blood was collected during exacerbations.ResultsSerum NFL levels were significantly increased after 2 years of NTZ treatment in pre-PML patients compared with NTZ-ctr. The prognostic performance of serum NFL levels to predict PML development at 2 years was similar in the NTZ-ctr group and replication cohort. Serum NFL levels also distinguished PML from MS relapses and were 8-fold higher during PML compared with relapses.ConclusionsThese results support the use of serum NFL levels in clinical practice to identify patients with relapsing-remitting MS at higher PML risk and to differentiate PML from clinical relapses in NTZ-treated patients.Classification of EvidenceThis study provides Class I evidence that serum NFL levels can identify NTZ-treated patients with MS who will develop PML with a sensitivity of 67% and specificity of 80%.

Published
2021
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